UCSD Scientists Develop Novel Way to Screen Molecules Using Conventional CDs and Compact Disk Players

Graphic showing how molecules attached to CDs in new technique can screen for proteins

Chemists at the University of California, San Diego have developed a novel method of detecting molecules with a conventional compact disk player that provides scientists with an inexpensive way to screen for molecular interactions and a potentially cheaper alternative to medical diagnostic tests.

A paper detailing their development will appear this week in an advance on-line edition of the Journal of Organic and Biomolecular Chemistry and in the printed journal’s September 21st issue.

“Our immediate goal is to use this new technology to solve basic scientific questions in the laboratory,” says Michael Burkart, an assistant professor of chemistry and biochemistry at UCSD and a coauthor of the paper. “But our eventual hope is that there will be many other applications. Our intention is to make this new development as widely available as possible and to see where others take the technology.”

Burkart and James La Clair, a visiting scholar in Burkart’s laboratory who initially developed and patented the technique, said that since scientific laboratories often rely on laser light to detect molecules, it made sense to them to design a way to detect molecules using the most ubiquitous laser on the planet–the CD player.

“The CD is by far the most common media format in our society on which to store and read information,” says La Clair. “It’s portable, you can drop it on the floor and it doesn’t break. It’s easy to mass produce. And it’s inexpensive.”

Their technique takes advantage of the tendency for anything adhering to the CD surface to interfere with a laser’s ability to read digital data burned onto the CD.

“We developed a method to identify biological interactions using traditional compact disk technology,” explains La Clair, who provided the patent rights to the method to UCSD. “Using inkjet printing to attach molecules to the surface of a CD, we identified proteins adhering to these molecules by their interaction with the laser light when read by a CD player.”

While usually anything, like a scratch on the CD surface, that would interfere with the detection of the bits of information encoded on a CD would be a drawback, the UCSD researchers actually exploited this error to detect molecules.

“That’s the novelty of this,” Burkart points out. “We are actually using the error to get our effect.”

The typical CD consists of a layer of metal sandwiched between a layer of plastic and a protective lacquer coating. When a CD is burned, a laser creates pits in the metal layer. A CD player uses a laser to translate the series of pits and intervening smooth surface into the corresponding zeros and ones that make up the bits of digital information.

To do molecular screening, the researchers took a CD encoded with digital data, and enhanced the chemical reactivity of the plastic on the readable surface. They then added molecules they wanted to attach to this surface to the empty ink wells of an inkjet printer cartridge and used the printer to “print” the molecules onto the CD. This resulted in a CD with molecules bound to its readable surface in specific locations relative to the pits in the metal layer of the CD encoding the digital information. When the CD with these molecules attached is placed in a CD player, the laser detects a small error in the digital code relative to what is read from the CD without the molecules attached.

To detect proteins or other large molecules in a solution like a blood sample, the modified CD is allowed to react with the sample solution. Like a key that only fits in a certain lock, some proteins bind to specific target molecules. Thus, specific molecules on the surface of a CD can be used to “go fishing” for certain proteins in a sample. The attachment of these proteins will introduce further errors into the reading of the CD. Furthermore, since the molecules on the surface of the CD are at known locations relative to the bits of encoded information, the errors tell the researchers what molecules have attached to their target protein and, thus, whether or not that protein is present in the sample.

“James has even done this using CDs with music, like Beethoven’s Fifth Symphony,” says Burkart. “And you can actually hear the errors.”

“How many people on this planet can actually hear a molecule attached to another molecule?” asks La Clair.

While a few bugs need to be ironed out before the technique can be used to accurately quantify the amount of a given protein in solution, Burkart plans to apply it immediately to help him screen for new compounds in his natural products chemistry research laboratory. Compared to the $100,000 price tag for a fluorescent protein chip reader, he points out, a CD player costs as little as $25.

The researchers envision many other potential applications for this technology outside the laboratory, particularly in the development of inexpensive medical diagnostic tests, now beyond the means of many people around the world, particularly in developing countries.

“In theory, anyone who has a computer with a CD drive could do medical tests in their own home,” says La Clair.

The researchers hope that by openly publishing their development in the scientific literature, others will customize the technology in a variety of ways, eventually leading to a wide range of inexpensive new diagnostic kits and other beneficial

products.

“We plan to make this fully available and see what people come up with,” says Burkart.

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